Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Reexamination Certificate
2002-10-16
2004-10-19
Nazario-Gonzalez, Porfirio (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
C502S155000, C526S943000
Reexamination Certificate
active
06806377
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to methods for the synthesis of metallocenes.
BACKGROUND OF THE INVENTION
Amino-functionalised titanocenes are of increasing interest because of their potential to act as highly active and selective olefin polymerisation catalyst precursors [1,2,3,4]. The neutral amino function can reversibly co-ordinate to the metal centre, potentially stabilising highly reactive intermediates formed during homogeneous catalytic processors. High catalytic activity has been found with group IV metallocenes as well as with metallocenes involving other metals. For instance, half-sandwich complexes of chromium in which the pendant amino function is co-ordinated to the metal centre have been shown to be highly active olefin polymerisation catalysts [5]. Furthermore, the pendant amino function can interact with inorganic support materials, thereby incorporating traditional metallocene catalysts into heterogeneous catalysts.
Quaternisation of the pendant amino group can result in water stable and soluble species [1,2,4]. Such species may not only provide water soluble catalytic compounds but are also useful as anti-tumour drugs having advantages over the known anti-tumour drug titanocene dichloride. Although titanocene dichloride is an efficient anti tumour agent [6,7], it has low solubility and is unstable in aqueous solution. The greater stability and solubility of amino-functionalised titanocenes renders these materials, and their dihydrochloride derivatives, potentially more suitable as anti-tumour agents as well as providing more suitable models for studying the mechanism of action of titanocene dichloride as an anti tumour agent
Known synthetic methods for the preparation of the dihydrochloride salts of amino-functionalised titanocenes involve the deprotonation of the neutral cyclopentadiene to give lithium, sodium or thallium salts [2,3,4]. In situ deprotonation can be achieved by the addition of an external base [8]. The reaction of the metal salt with TiCl
4
results from the formation of the neutral metallocene which is then reacted with HCl to give the dihydrochloride salt Accordingly such a process involves 3 steps from the cyclopentadiene to the dihydrochloride salt. There is a need for an improved process involving fewer steps and producing the dihydrochloride salt in relatively high yield.
STATEMENTS OF INVENTION
According to the present invention there is provided a method for the preparation of a metallocene halide salt having at least one cyclopentadiene group substituted by a basic group, said method comprising reacting together a metal halide with a cyclopentadiene substituted by said basic group.
Accordingly the present invention provides a single step process for the preparation of an amino-functionalised metallocene which can be produced in high yield. It is believed that this single step process is possible because the method utilises the presence of an “internal base” rather than by making use of an external base in the known 3 step process.
The method of the present invention may be applied to the preparation of metallocenes of both early and late transition metals including the group IV metals Ti, Zr and Hf.
Preferably the metal halide is a homoleptic halide, more preferably a homoleptic chloride, an example being TiCl
4
.
Preferably the substituted cyclopentadienyl carries a pendant Lewis base. More preferably the Lewis base is provided by an amino group, for instance, a tertiary amino group, examples being —CH
2
CH
2
N(CHCH
3
)
2
and —CH
2
CH
2
N(CH
2
)
5
.
Preferably the cyclopentadienyl is contacted with the metal halide in the presence of an inert solvent such as toluene.
Preferably the substituted cyclopentadiene and the metal halide are reacted together at ambient temperature or below. One reactant may be added to the other in a dropwise fashion. The addition may be carried out more quickly the lower the temperature.
The metallocene halide salt prepared by the method of the present invention may be converted to the neutral metallocene by contacting the salt with a base. Furthermore the metallocene halide salt may be converted to other species. For example, contacting the metallocene halide salt with an alkylating agent results in the formation of an alkyl substituted metallocene.
The method of the present invention represents a new and facile route to metallocene halide salts in high yield. The method is therefore highly advantageous over the known three steps synthetic routes.
REFERENCES:
patent: 2777002 (1957-01-01), Sullivan
patent: 3920757 (1975-11-01), Watson
patent: 4851430 (1989-07-01), Köpf-Maier et al.
patent: 5002969 (1991-03-01), Köpf-Maier et al.
patent: 6100414 (2000-08-01), Li et al.
patent: 19630580 (1998-02-01), None
Blais et al., “Pendent Aminoalkyl-Substituted Monocyclopentadienyltitanium Compounds and Their Polymerization Behavior,”Organometallics, 17: 3775-3783 (1998).
Jutzi et al., “Titanium and Zirconium Bent-Sandwich Complexes with the New [2-(Diisopropylamino)ethyl]cycolpentadienyl Ligand: Catalysts for the Polymerization of Ethylene and the Dehydrocoupling of Phenylsilance,”Organometallics15: 4153-4161 (1996).
Jutzi et al., “Aminoethyl-Functionalized Cyclopentadienyl Complexes of d-Block Elements,”Eur. J. Inorg. Chem., 663-674 (1998).
P. Köpf-Maier,Antitumor Bis(cyclopentadienyl)metal Complexes: Antitumor Metallocenes, 261-296.
Toney et al., “Hydrolysis Chemistry of the Metallocene Dichlorides M(&eegr;5-C5H5)2Cl2, M=Ti, V, Zr. Aqueous Kinetics, Equilibria, and Mechanistic Implications for a New Class of Antitumor Agents,”J. Am. Chem. Soc.,107: 947-953 (1985).
Herrmann et al., “Cyclische Amine als intramolekulare Hilfsliganden in &pgr;-Komplexen des Titans,”Journal of Organometallic Chemistry, 486:291-295 (1995).
Jutzi, P. & Kleimeier, J., “Der (N,N-Dimethylaminoethyl)cyclopentadienyl-Ligand in der Komplexchemie von Titan and Zirkon,”Journal of Organometallic Chemistry, 486: 287-289 (1995).
Sinnema et al., “Titanium Dichloro, Bis(carbyl), Aryne, and Alkylidene Complexes Stabilized by Linked Cyclopentadienyl-Amido Auxiliary Ligands,”Organometallics, 16: 4245-4247 (1997).
McGowan Margaret Dymphna
McGowan Patrick Columba
Myers Bigel & Sibley Sajovec, PA
Nazario-Gonzalez Porfirio
The University of Leeds
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